KINETICS OF RETINOID METABOLISM BY ALCOHOL DEHYDROGENASE

视黄醇(维生素A)，在胃肠道中产生 摄入β-胡萝卜素，在肝脏被氧化成视网膜。视网膜 对夜视很重要，维甲酸，以及 视网膜在细胞发育中起着重要的作用。视黄醇、视黄醇和 维甲酸是维甲酸的一类，而维甲酸的水平是 与胎儿酒精综合征和夜盲相关的影响 与酗酒有关。据推测，人类 胃和肝脏的胞浆酒精脱氢酶同工酶 在类维A酸代谢中起生理酶的作用 摄入的乙醇会干扰这一过程。这两个项目的目的是- 一年的探索性建议是确定使用的可行性 稳态、停流和快速扫描动力学以及计算机 模拟来验证这一假说。一组动力学数据将是 描述了全反式维甲酸和 11-顺式维甲酸在肝脏和胃乙醇脱氢酶中的代谢 37摄氏度的同工酶。在细胞内，维甲酸被运输 通过一类称为细胞维甲酸结合蛋白的结合蛋白 (CRBP)。CRBP以及乙醇和乙醛在 类维甲酸代谢所受的酒精脱氢酶同工酶也会 已评估。这些动力学数据将用于执行一系列 以计算机为基础的模拟实验，考察了 类维A酸代谢的酶、底物和产物。这些实验 将有助于确定人类胞浆的作用 肝脏和肝脏中维甲酸代谢中的乙醇脱氢酶同工酶 胃肠道，并将评估乙醇在 这些酶对类维甲酸代谢的干扰。

Retinol (vitamin A), produced in the gastrointestinal tract after ingestion of beta-carotene, is oxidized to retinal in the liver. Retinal is important for night vision, and retinoid acid, and product of retinal, is important in cell development. Retinol, retinal, and retinoid acid are among a class of retinoids, and retinoid levels are correlated with fetal alcohol syndrome and night blindness, effects associated with alcoholism. It has been hypothesized that human cytosolic alcohol dehydrogenase isoenzymes in the stomach and liver function as physiological enzymes in retinoid metabolism, and that ingested ethanol interferes with this process. The purpose of this two- year exploratory proposal is to determine the feasibility of using steady-state, stopped-flow, and rapid scanning kinetics, and computer simulation to test this hypothesis. A set of kinetic data will be collected that describes the individual steps of all-trans-retinoid and 11-cis-retinoid metabolism by liver and gastric alcohol dehydrogenase isoenzymes at 37 degrees Celsius. In the cell, retinoids are transported by a class of binding proteins called cellular retinoid binding proteins (CRBP). The role of CRBP, as well as of ethanol and acetaldehyde, in retinoid metabolism by the alcohol dehydrogenase isozymes will also be evaluated. These kinetics data will be used to perform a series of computer-based simulation experiments that investigate the effect of enzyme, substrate, and product of retinoid metabolism. These experiments will contribute to efforts in identifying the role of human cytosolic alcohol dehydrogenase isoenzymes in retinoid metabolism in the liver and gastrointestinal tract, and will evaluate the role of ethanol in the perturbation of retinoid metabolism by these enzymes.